Malfunction of the endothelial cell layer results in corneal thickening, and eventually the loss of corneal transparency. Currently, penetrating keratoplasty is widely used to replace the diseased endothelium. Disadvantages of the procedure include high corneal astigmatism, sundry suture complications and a weak graft-host junction that is susceptible to wound dehiscence. A posterior lamellar keratoplasty, which replaces only the diseased endothelium and a modicum of pre-Descemet's stroma can avert these problems, however, the difficulty of surgery using traditional surgical instruments limits the use of these procedures to a very few highly skilled surgeons. Novel femtosecond laser surgical technology is capable of creating high precision corneal resections with clinically negligible collateral damage to adjacent tissue and without opening cuts or damage at the anterior corneal surface. Femtosecond laser energy can be delivered through transparent and semitransparent cornea and focused at any depth beneath the corneal anterior surface. Tissue resection is achieved by scanning the focal spot of the femtosecond laser along a predetermined pattern inside the corneal stroma. A layer of microbubbles is created by femtosecond photodisruptions, which separates the tissue. The technology is now FDA cleared for cutting corneal flaps and anterior corneal grafts. We propose to develop new procedures to replace the diseased endothelial cell layer using femtosecond laser to cut posterior corneal grafts in both the donor and host corneas. Novel host-donor tissue contact geometries, including self-locking wound edges, are predicted to enhance wound healing. Diseased posterior cornea is removed through a small side incision at the limbus. The donor graft is inserted into the lamellar interface through the same incision and held in position with air injected into the anterior chamber. To optimize refractive outcomes and self-locking or self-sealing wound edges we propose to model the biomechanics of the postoperative cornea and confirm these results with in vivo animal experiments. Finally, we propose in vivo experiments in animals with non-regenerating endothelium to study the physiology and biomechanics of the postoperative corneas as a function of graft geometry and time. Successful completion of this project will contribute to the understanding of corneal biomechanics and physiology after femtosecond laser posterior lamellar keratoplasty. The project introduces a precision microsurgical technique for replacing diseased endothelium with potentially accelerated recovery and improved visual outcomes.